Using Tenecteplase to treat Central Retinal Artery Occlusion

TENecteplase in Central Retinal Artery Occlusion Study (TenCRAOS): A Randomized Placebo-controlled Trial of Early Systemic Tenecteplase Treatment in Patients With Central Retinal Artery Occlusion.

This study is testing if a medication called Tenecteplase can help improve vision in people who have a blocked artery in the eye when given soon after symptoms start.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 78 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Oslo University Hospital (Academic / other)
• Locations: 29 sites (Melbourne and 28 other locations)
• Trial ID: NCT04526951 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of Tenecteplase, a thrombolytic agent, in treating patients with Central Retinal Artery Occlusion (CRAO) when administered within 4.5 hours of symptom onset. It is a phase 3, randomized, double-blind, and multi-center trial comparing Tenecteplase to Acetylsalicylic Acid (ASA) in a 1:1 ratio. Patients will be monitored in stroke units and assessed for visual acuity improvements at 30 and 90 days post-treatment. The study aims to provide evidence on whether early systemic thrombolysis can enhance visual outcomes in CRAO patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with non-arteritic CRAO symptoms lasting less than 4.5 hours and a visual acuity of ≥ 1.0 logMAR.

Not a fit: Patients with other active interventions targeting CRAO or specific ocular conditions such as branch retinal artery occlusion or proliferative diabetic retinopathy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve visual outcomes and reduce the risk of permanent blindness in patients with CRAO.

How similar studies have performed: Previous studies have indicated that systemic thrombolysis may improve outcomes in CRAO, suggesting that this approach has potential based on observational data.

Eligibility criteria

Inclusion Criteria:

1. Non-arteritic central retinal artery occlusion with ≥ 1.0 logMAR visual acuitiy and symptoms lasting less than 4.5 hours.
2. Ability to administer the Investigator Medicinal Product (IMP) within 4.5 hours of symptom onset.
3. Age ≥18 years.
4. Informed written consent of the patient.
5. A woman of childbearing potential (WOCBP) must confirm that in her opinion, she cannot be pregnant, OR if there is a possibility that she is pregnant, a negative pregnancy test must be confirmed before any IMP is given.

Exclusion Criteria:

1. No other active intervention targeting CRAO.
2. Branch retinal artery occlusion, cilioretinal artery supplying the macula, combined arterial-venous occlusion, proliferative diabetic retinopathy, elevated intraocular pressure (\> 30 mmHg) or clinical suspicion of ophthalmic artery occlusion occlusion (e.g. choroidal nonperfusion, absence of cherry red spot, no light perception).
3. Systemic diseases; severe general diseases, systemic arterial hypertension (blood pressure \>185/110 mmHg), despite medical therapy, or clinical suspicion of acute systemic inflammation.
4. Presence of intracranial haemorrhage on brain MRI/CT.
5. Medical history: heart attack within the last 6 weeks, intracerebral bleeding or neurosurgical operation within the last 4 weeks, therapy with anticoagulation, allergic reaction to contrast agent, hemorrhagic diathesis, aneurysms, inflammatory vascular diseases (eg, giant cell arteritis, granulomatosis with polyangitis), endocarditis, or gastric ulcer.
6. No willingness and ability of the patient to participate in all follow-up examinations.
7. Pregnancy (if suspicion of pregnancy s-hCG or u-hCG must be negative).
8. Allergy or intolerance to any ingredients of IMP or placebo or gentamicin.
9. Other conditions / circumstances likely to lead to poor treatment adherence (eg, history of poor compliance, alcohol or drug dependency, no fixed abode).
10. Significant bleeding disorder either at present or within the past 6 months.
11. Effective oral anticoagulant treatment, eg, warfarin sodium (INR \>1.3).
12. Effective anticoagulant treatment with heparin or low molecular weight heparin the last 48 hours.
13. Any history of central nervous system damage (ie, neoplasm, aneurysm, intracranial or spinal surgery).
14. Known hemorrhagic diathesis.
15. Major surgery, biopsy of a parenchymal organ, or significant trauma within the past 2 months (this includes any trauma associated with acute myocardial infarction).
16. Recent non-compressible vessel puncture within 2 weeks.
17. Recent trauma to the head or cranium.
18. Prolonged cardiopulmonary resuscitation (\>2 minutes) within the past 2 weeks.
19. Acute pericarditis and/or subacute bacterial endocarditis.
20. Acute pancreatitis.
21. Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis.
22. Active peptic ulceration.
23. Arterial aneurysm and known arterial/venous malformation.
24. Neoplasm with increased bleeding risk.
25. Any known history of hemorrhagic stroke or stroke of unknown origin.
26. Known history of ischemic stroke or transient ischemic attack in the preceding 3 months.
27. Dementia.

Where this trial is running

Melbourne and 28 other locations

• St Vincent's Hospital Melbourne — Melbourne, Australia (Withdrawn)
• ULB-Hôpital Erasme — Anderlecht, Belgium (Withdrawn)
• University Hospital Antwerp — Antwerp, Belgium (Completed)
• UZ Brussel — Brussel, Belgium (Withdrawn)
• University Hospital Leuven — Leuven, Belgium (Completed)
• Aarhus University Hospital — Aarhus, Denmark (Completed)
• Bispebjerg University Hospital — Copenhagen, Denmark (Completed)
• Rigshospitalet University Hospital — Copenhagen, Denmark (Completed)
• Helsinki University Hospital — Helsinki, Finland (Completed)
• Turku University Hospital — Turku, Finland (Completed)
• Mater Misericordiae University Hospital — Dublin, Ireland (Withdrawn)
• Kauno Klinikos Kaunas — Kaunas, Lithuania (Completed)
• Respublican Vilnius University Hospital — Vilnius, Lithuania (Withdrawn)
• Vilnius University Hospital — Vilnius, Lithuania (Completed)
• Sørlandet Hospital Trust — Arendal, Norway (Withdrawn)
• Haukeland University Hospital — Bergen, Norway (Completed)
• Vestre Viken Hospital Trust Drammen — Drammen, Norway (Completed)
• Østfold Hospital Trust Kalnes, Dept of Ophthalmology — Grålum, Norway (Completed)
• Innlandet Hospital Trust — Lillehammer, Norway (Withdrawn)
• Nordmøre and Romsdal Regional Hospital — Molde, Norway (Withdrawn)
• Helse Nord Trøndelag Trust — Namsos, Norway (Completed)
• Oslo University Hospital — Oslo, Norway (Recruiting)
• Telemark Hospital Trust — Skien, Norway (Completed)
• Stavanger University Hospital — Stavanger, Norway (Withdrawn)
• University Hospital of North Norway, Tromsø — Tromsø, Norway (Withdrawn)
• St Olav University Hospital — Trondheim, Norway (Completed)
• Vestfold Hospital Trust — Tønsberg, Norway (Completed)
• Karolinska University Hospital — Stockholm, Sweden (Completed)
• Sundsvall Hospital — Sundsvall, Sweden (Withdrawn)

Study contacts

• Study coordinator: Anne Hege Aamodt

Conditions Central Retinal Artery Occlusion; thrombolysis tenecteplase